Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID‐19

The global pandemic of coronavirus disease 2019 (COVID‐19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID‐19 patients show elevated D‐dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI‐1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID‐19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre‐existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue‐type plasminogen activator (tPA), to treat COVID‐19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID‐19 patients to degrade fibrin and improving oxygenation in critically ill patients.     

Bifidobacterium Species Colonization in Infancy: A Global Cross-Sectional Comparison by Population History of Breastfeeding

Bifidobacterium species are beneficial and dominant members of the breastfed infant gut microbiome; however, their health benefits are partially species-dependent. Here, we characterize the species and subspecies of Bifidobacterium in breastfed infants around the world to consider the potential impact of a historic dietary shift on the disappearance of B. longum subsp. infantis in some populations. Across populations, three distinct patterns of Bifidobacterium colonization emerged: (1) The dominance of Bifidobacterium longum subspecies infantis, (2) prevalent Bifidobacterium of multiple species, and (3) the frequent absence of any Bifidobacterium. These patterns appear related to a country’s history of breastfeeding, with infants in countries with historically high rates of long-duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter-duration breastfeeding. In addition, the timing of infant colonization with B. longum subsp. infantis is consistent with horizontal transmission of this subspecies, rather than the vertical transmission previously reported for other Bifidobacterium species. These findings highlight the need to consider historical and cultural influences on the prevalence of gut commensals and the need to understand epidemiological transmission patterns of Bifidobacterium and other major commensals.     

Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers

A combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine’s unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.Subject terms: Medical research, Developmental biology     

Intersectionality as an Analytic Framework for Understanding the Experiences of Mental Health Stigma Among Racialized Men

International Journal of Mental Health and Addiction - The objective of this research was to use intersectionality to explore Asian men’s experiences of stigma and mental illness to tease out...     

AIDS virus infection and autoimmunity: a perspective of the clinical, immunological, and molecular origins of the autoallergic pathologies associated with HIV disease

The acquired immune deficiency syndrome (AIDS) is a viral-induced disorder of humans that is reaching pandemic proportions. The etiologic agent responsible for AIDS is recognized as a retrovirus termed the human immunodeficiency virus (HIV). This virus is both cytotropic and cytopathic for T lymphocytes in vitro, and patients with AIDS and HIV-related conditions invariably have serious T cell abnormalities, notably a reduced number of the helper/inducer (CD4+) subpopulation. There is now a substantial body of evidence to suggest that the AIDS virus triggers a diverse range of autoimmune phenomena. The purpose of this article is to summarize the clinical and immunopathological manifestations of autoimmunity in HIV infection and to provide a perspective of the possible origins and roles autoimmune reactions play in HIV disease progression.     

培养心肌细胞牵张刺激装置的建立及应用

1　方法　牵张刺激装置的制作如模式图 1.制作实验模型采用材料为有机玻璃板、2 4孔培养板、硅胶膜 (厚度 0 .2 2 μｍ) .硅胶膜从平面圆形变为球形时 ,面积扩大的百分比 =(Ｓ球 -Ｓ园 ) /Ｓ园 ,其中Ｓ球 =ＡＤ2 ,Ｓ园 =ｒ2 ,而ＡＤ2 =ｈ2 +ｒ2 ,其中ｒ为孔的半径 ,ｈ为膜升高的高度图 2 .通过控制ｈ的大小 ,可控制膜被牵拉的强度 .本实验采用使膜面积扩大 2 0 %的强度 ,故ｈ =4ｍｍ[1] .参照Ｋａｓｓｉｒｉ等[2 ,3 ] 方法进行心肌细胞的分离培养 .生长有贴壁心肌细胞的 2 4孔板被固定于牵张装置 ,缓慢充气使硅胶膜向上凸起 4ｍｍ ,分别维持…     

ASO Visual Abstract: Impact of Endocrine Therapy Adherence on Outcomes in Elderly Women With Early-Stage Breast Cancer Undergoing Lumpectomy Without Radiotherapy

Annals of Surgical Oncology -     

Increased risk of renal dysfunction with percutaneous mechanical thrombectomy compared with catheter-directed thrombolysis

Objective

Percutaneous mechanical thrombectomy (PMT) is regularly used in the treatment of both venous and arterial thrombosis. Although there has been no formal report, PMT has been linked to cases of reversible postoperative acute kidney injury (AKI). The purpose of this study is to evaluate the risk of renal dysfunction in patients undergoing PMT vs catheter-directed thrombolysis (CDT) for treatment of an acute thrombus.